Attacking Alzheimer’s: A Conversation with Jim Sullivan

Jim Sullivan, vice president for discovery at AbbVie, explains why Alzheimer’s disease is so difficult to treat, what AbbVie is doing to target the disease, and why the need for treatments for all types of dementia is growing exponentially.

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Jim Sullivan, vice president for discovery at AbbVie

Why Alzheimer's?

Nearly 47 million people worldwide are living with dementia — and over the next few decades that number is projected to double every 10 to 15 years. Alzheimer’s is the most common form of dementia, and aging is its biggest risk factor. If we all live to the age of 85, one in two of us will develop dementia.

So, Alzheimer’s represents a huge challenge for society as the number of patients and caregivers seeking help from the health care system explodes in the coming decades. Just as importantly, from an R&D perspective there have been a number of significant advances in our understanding of the disease. This coupled with the availability of new imaging tools that are helping us better understand the disease and also investigate potential treatments, present us with promising scientific opportunities.

Brain of an Alzheimer patient (at left) compared with a normal brian (at right). The Alzheimer's disease brain (red) is considerably shrunken.

How is it treated today?

It’s not. Treatments available at the moment simply address the cognitive symptoms and do nothing to prevent the progression of the disease or reverse the damage. So while these treatments may work for a while, giving the patients a “bump” in cognition, their effect quickly wears off. This is because the disease continues to progress and patients reach a point when they don’t have enough healthy neurons for the treatments to act on.

How has Alzheimer's research progressed over the years?

More than 100 years ago, pathologist Alois Alzheimer examined the brains of people with dementia and discovered clumps of protein in the cortex and the hippocampus. Known as amyloid plaques, those clumps make up another protein called beta-amyloid. A second crucial discovery, made decades later, was the identification of the protein called tau that forms tangles throughout the brain.
Very recently we discovered that the formation of these beta-amyloid plaques and tangles starts to occur when people are as young as in their 40s. This process begins fairly slowly, but it is constant and unrelenting. Over time, the accumulation of amyloid and tangles disrupts the way neurons communicate with each other, ultimately causing their death. That’s when you see the symptoms of the disease.

There have been a number of other scientific breakthroughs that have occurred during the last five to 10 years. For example, genetic studies have pointed to a role of the immune system in lipid metabolism in the progression of the disease. It is all these breakthroughs that make this a good time to invest in this area.

Alzeimer's disease brain cell. The tangle (green) lies in the cytoplasm (blue) of the cell, and consists of abnormal aggregates of the protein tau. In the healthy cell, tau stablizes microtubes in the cytoplasm.

So the damage is done long before the patient becomes symptomatic?

Exactly. In heart disease, we know enough to identify warning signs, like elevated cholesterol, and can treat before the patient is symptomatic. With Alzheimer’s this is not the case.

We know now that there is a pre-symptomatic phase when patients don’t show cognitive decline that could last for up to 10 years or more. So when patients start showing mild cognitive impairment, for example forgetting words, it indicates significant damage. Over time, moderate cognitive impairment becomes severe. This is when patients start showing the signs of severe dementia and the behaviors associated with it, like agitation and aggression.

How are you looking at treating Alzheimer’s?

We are taking advantage of the recent scientific insights to identify innovative new approaches.

For example, we’re targetting tau.  

Many patients with Alzheimer’s have significant accumulation of tau so we’re looking at how we can potentially block this accumulation and spreading early on in the disease.

We are currently collaborating with one of the world’s leading Alzheimer’s researchers, Dr. David Holtzman and his group, from the Washington University in St. Louis, Missouri, who identified an antibody that blocks the spreading of tau. 

Many companies have been getting away from pursuing Alzheimer’s treatments. Why jump into a field that others are avoiding?

Our understanding of Alzheimer’s has increased significantly in recent years. There are new tools available — imaging and biomarkers — that can help us not only understand the disease but also identify patients and evaluate the effects of potential drugs early in clinical development.

Additionally, we are recruiting world-class experts. Dr. Eric Karran, a renowned Alzheimer’s researcher and leading figure in the area, has just joined us, and we’ll be collaborating with some of the leading academic labs in various areas of Alzheimer’s biology.

Finding new treatments for Alzheimer’s has enormous potential to make a remarkable impact on people’s lives – both the lives of patients and also those of their caregivers. That’s why we’re committed to investing in this research for the long term.

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